in Table 1 [see Warnings and Precautions (5.3)]. A starter packshould be used for patients who will be titrated to the 2-mg maintenance dosage [see How Supplied/Storage and Handling(16.1, 16.2)].
Table 1 Dose Titration Regimen to Reach MAYZENT 2 mg Maintenance Dosage
Titration Titration Dose Titration Regimen
Day 1 0.25 mg 1 x 0.25 mg
Day 2 0.25 mg 1 x 0.25 mg
Day 3 0.50 mg 2 x 0.25 mg
Day 4 0.75 mg 3 x 0.25 mg
Day 5 1.25 mg 5 x 0.25 mg
If one titration dose is missed for more than 24 hours, treatment needs to be reinitiated with Day 1 of the titration regimen.
2.3 Recommended Dosage in Patients With CYP2C9 Genotypes *1/*3 or *2/*3
Maintenance Dosage
In patients with a CYP2C9*1/*3 or *2/*3 genotype, after treatment titration (see Treatment Initiation), the recommendedmaintenance dosage of MAYZENT is 1 mg taken orally once daily starting on Day 5.
Treatment Initiation
Initiate MAYZENT with a 4-day titration, as shown in Table 2 [see Warnings and Precautions (5.3) and Use in SpecificPopulations (8.6)]. Do not use the starter pack for patients who will be titrated to the 1-mg maintenance dosage.
Table 2 Dose Titration Regimen to Reach MAYZENT 1 mg Maintenance Dosage
Titration Titration Dose Titration Regimen
Day 1 0.25 mg 1 x 0.25 mg
Day 2 0.25 mg 1 x 0.25 mg
Day 3 0.50 mg 2 x 0.25 mg
Day 4 0.75 mg 3 x 0.25 mg
If one titration dose is missed for more than 24 hours, treatment needs to be reinitiated with Day 1 of the titration regimen.
2.4 First Dose Monitoring in Patients With Certain Preexisting Cardiac Conditions
Because initiation of MAYZENT treatment results in a decrease in heart rate (HR), first-dose 6 hour monitoring isrecommended for patients with sinus bradycardia [HR less than 55 beats per minute (bpm)], first- or second-degree[Mobitz type I] AV block, or a history of myocardial infarction or heart failure [see Warnings and Precautions (5.3) andClinical Pharmacology (12.2)].
First Dose 6-Hour Monitoring
Administer the first dose of MAYZENT in a setting where resources to appropriately manage symptomatic bradycardiaare available. Monitor patients for 6 hours after the first dose for signs and symptoms of bradycardia with hourly pulseand blood pressure measurement. Obtain an ECG in these patients at the end of the Day 1 observation period.
Additional Monitoring After 6-Hour Monitoring
If any of the following abnormalities are present after 6 hours (even in the absence of symptoms), continue monitoringuntil the abnormality resolves:
The heart rate 6 hours postdose is less than 45 bpm
The heart rate 6 hours postdose is at the lowest value postdose, suggesting that the maximum pharmacodynamic effect
on the heart may not have occurred
The ECG 6 hours postdose shows new onset second-degree or higher AV block
If postdose symptomatic bradycardia, bradyarrhythmia, or conduction related symptoms occur, or if ECG 6 hours postdoseshows new onset second degree or higher AV block or QTc greater than or equal to 500 msec, initiate appropriatemanagement, begin continuous ECG monitoring, and continue monitoring until the symptoms have resolved if nopharmacological treatment is required. If pharmacological treatment is required, continue monitoring overnight and repeat6-hour monitoring after the second dose.
Advice from a cardiologist should be sought to determine the most appropriate monitoring strategy (which may includeovernight monitoring) during treatment initiation, if treatme |
